Ultra-sensitive and selective quantification of endothelin-1 in human plasma using ultra-performance liquid chromatography coupled to tandem mass spectrometry

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide and the plasma concentrations are commonly quantified by immunoassays such as enzyme-linked immuno-sorbent assays (ELISA) with the disadvantage of possible cross-reactivity with closely related endothelin derivatives. The aim of this...

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Hauptverfasser: Suzuki, Yosuke (VerfasserIn) , Witt, Lukas (VerfasserIn) , Mier, Walter (VerfasserIn) , Mikus, Gerd (VerfasserIn) , Markert, Christoph (VerfasserIn) , Haefeli, Walter E. (VerfasserIn) , Burhenne, Jürgen (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2017
In: Journal of pharmaceutical and biomedical analysis
Year: 2017, Jahrgang: 142, Pages: 84-90
ISSN:1873-264X
DOI:10.1016/j.jpba.2017.04.038
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1016/j.jpba.2017.04.038
Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0731708517305319
Volltext
Verfasserangaben:Yosuke Suzuki, Lukas Witt, Walter Mier, Gerd Mikus, Christoph Markert, Walter E. Haefeli, Jürgen Burhenne

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520 |a Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor peptide and the plasma concentrations are commonly quantified by immunoassays such as enzyme-linked immuno-sorbent assays (ELISA) with the disadvantage of possible cross-reactivity with closely related endothelin derivatives. The aim of this study was to develop and validate an ultra-sensitive and selective assay for the quantification of ET-1 in human plasma, using ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) after solid phase extraction. The assay fulfilled the requirements of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) guidelines for assay validation, with a lower limit of quantification of 1.5pg/mL for ET-1. Recovery rates from plasma ranged between 80.8% and 93.6%, and matrix effect varied between 121% and 135%. The assay was successfully applied to assess the time course of plasma ET-1 concentrations in two human volunteers after co-administration of bosentan and clarithromycin. In this trial, the concentrations measured by UPLC-MS/MS were slightly lower than those measured by ELISA, with a strong positive correlation between the two methods. Our novel UPLC-MS/MS method is applicable to the clinical setting and may have better selectivity for ET-1 than ELISA. 
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